Ulcerative colitis and Crohn's disease are collectively called inflammatory bowel disease (IBD), and are both unexplained refractory diseases having a predilection for the juvenile to adolescent people and repeating recrudescence. In Japan, ulcerative colitis and Crohn's disease have been listed as diseases for specified disease treatment research since 1975 (October, Showa 50) and 1976 (October, Showa 51), respectively. The number of patients with these diseases tends to increase in Japan, and among them, that of those with ulcerative colitis is more than 100,000. A peak of age at onset is seen between the late-10s and the early-30s; however, onset in advanced age has also increased. Because more common in young people, the diseases greatly interfere with social life such as academic life, working, and marriage; the goal of treatment of the diseases is to control the disease state to enable the continuance of normal social life, under present circumstances in which they are of unknown cause and has no radical cure.
The disease state of ulcerative colitis is classified according to the diseased area and the course and severity thereof; it is classified into “proctitis type”, “left-side colitis type”, and “whole colitis type” by area and into “fulminant”, “severe”, “moderate”, and “mild” depending on clinical manifestation by severity. On the other hand, Crohn's disease can occur all over the alimentary tract; thus, its symptom is diverse and these symptoms are sometimes intermittently seen. It is classified by lesion area into “small bowel type”, whose lesions are present only in the small bowel, “large bowel type”, whose lesions are present only in the large bowel, and “small-bowel/large-bowel type”, whose lesions are present in both of these areas. It may be classified by lesion type into “inflammation type”, “narrowing type”, and “perforation type”; the latter shows more intractable nature and is clinically problematical. The severe case and the mild case greatly differ in symptoms; the symptoms are intense in an active stage (advanced stage) during which inflammation is intense, and the symptoms abate in a remission stage during which the inflammation abates. However, the narrowing, perforation, and fistulae cannot be restored, and the symptoms do not disappear in the remission stage. In addition, there are relative diseases, such as non-specific multiple small-bowel ulcer and bowel Behcet's disease, which not infrequently show intractable nature.
In Japan, both ulcerative colitis and Crohn's disease are treated according to guidelines prepared by a study group of the Ministry of Health, Labour and Welfare. Specifically, systemic administration/local administration of a steroid preparation, blood component removal therapy, immunosuppressant therapy, biological product therapy, and the like are performed on the basis of an aminosalicylic acid preparation and nutrition therapy. Steroid therapy is effective for the remission induction treatment of an inflammatory bowel disease; however, side effects due to long-term steroid therapy and their attendant reduction in QOL are seen as a problem. Although steroid therapy should be reduced to minimum necessary, cases exist in which a sufficient effect is not obtained by another treatment method (an aminosalicylic acid preparation). Particularly, elderly people are at risk of having complication of severe infection associated with the use of a steroid drug, an immunosuppressant, or a biological product; the use of these drugs is restricted.
In addition, for ulcerative colitis, “steroid-resistant cases” not responsive to steroid therapy exerting the strongest treatment effect or “steroid-dependent cases” in which the effect of steroid therapy is obtained but recrudescence occurs during the tapering of steroid exist in no small numbers, and have become problematical as “intractable” ulcerative colitis. Adverse events due to long-term use of steroid have become a problem; thus, it is important how remission can be maintained by treatment not relying on steroid. Patients with intractable inflammatory bowel disease sometimes become relative candidates for surgery since the excessive administration of steroid or the maintenance of remission is difficult, which markedly impairs QOL, and existing steroid therapy and immunosuppressant therapy have limitations; thus, a new treatment strategy is necessary. For Crohn's disease, a high remission-inducing effect of a biological product (an anti-TNF-α agent) has been observed in recent years; however, as for a long-term remission-maintaining effect, it has turned out that the agent alone cannot maintain remission in about half of patients. Although the effect of a combination of an immunosuppressant therewith has also been studied, reports of occurrence of malignant lymphoma have been increasing; thus, there is need for the development of a new treatment strategy other than a biological product and an immunosuppressant. Unexplained relative diseases having difficulties in treatment also exist, such as non-specific multiple small-bowel ulcer and bowel Behcet's disease; however, treatment methods for these diseases have not been established.